Impact of Preoperative Environmental Enrichment on Prevention of Development of Cognitive Impairment following Abdominal Surgery in a Rat Model

2015 ◽  
Vol 123 (1) ◽  
pp. 160-170 ◽  
Author(s):  
Takashi Kawano ◽  
Satoru Eguchi ◽  
Hideki Iwata ◽  
Takahiko Tamura ◽  
Naoko Kumagai ◽  
...  
Keyword(s):  
Abdominal Surgery ◽  
Environmental Enrichment ◽  
Ex Vivo ◽  
Recovery Period ◽  
Postoperative Cognitive Dysfunction ◽  
Aged Rats ◽  
Novel Object ◽  
Young Rats ◽  
Age Related ◽  
Object Preference

Abstract Background: Sustained neuroinflammation may contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Here, the authors evaluated the preventive effect of preoperative environmental enrichment (PEE) on the development of neuroinflammation and concomitant POCD in a rat abdominal surgery model. Methods: Young and aged rats were assigned to one of four groups using a 2 × 2 experimental design: PEE versus sedentary condition for 14 days, by abdominal surgery versus anesthesia alone (n = 8 in each group). After a 7-day postsurgical recovery period, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of proinflammatory cytokines. Under identical conditions, microglia were isolated from the hippocampus for assessment of cytokine response to lipopolysaccharide. Results: In the sedentary group, aged, but not young, rats receiving surgery showed memory deficits (novel object preference during testing phase of 54.6 ± 7.8% vs. 76.9 ± 11.3% in nonsurgery group, P < 0.05) and increased hippocampal levels of cytokines compared with nonsurgical rats. PEE had no effects on novel object preference in nonsurgery animals (78.6 ± 10.7%), whereas it attenuated surgery-induced impairment of novel object preference (70.9 ± 15.0%, P < 0.05 vs. sedentary/surgery group) as well as increase of cytokine levels in hippocampus. Furthermore, upon ex vivo stimulation with lipopolysaccharide, cytokines release from hippocampal microglia isolated from aged rats before intervention was significantly higher in comparison with young rats. PEE resulted in reduction of these age-related microglial phenotypic changes. Conclusions: PEE could prevent the development of neuroinflammation and related POCD in aged rats by reversion of a proinflammatory phenotype of hippocampal microglia.

Effect of age on cerebral venous circulation disturbances in the rat

2000 ◽  
Vol 93 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Hiroyuki Otsuka ◽  
Hiroyuki Nakase ◽  
Kiyoshi Nagata ◽  
Katsuhiro Ueda ◽  
Oliver Kempski ◽  
...  
Keyword(s):  
Venous Occlusion ◽  
Aged Rats ◽  
Venous Flow ◽  
Content Type ◽  
Young Rats ◽  
Venous Circulation ◽  
Age Related ◽  
Venous Infarct ◽  
Group A ◽  
Fine Print

Object. Mild cerebral venous circulation disturbances (CVCDs) in aged patients are frequently known to cause unexpectedly severe postoperative complications in neurosurgical practice. The object of the present study was to determine whether there are age-related differences involved in vulnerability to CVCDs.Methods. Thirty-eight male Wistar rats were used. A single cortical vein with a 100-µm diameter was occluded photochemically by using rose bengal dye and fiberoptic illumination in young (Group Y, 19 animals aged 10–14 weeks) and aged (Group A, seven animals aged 80–100 weeks) rats. Five young and seven aged animals served as sham-operated controls. Regional cerebral blood flow (rCBF) was determined from local CBF, which was measured at 25 (5 × 5) identical locations, with the occluded vein located central to the scanning field, by using a laser Doppler scanning technique every 15 minutes for 90 minutes after venous occlusion. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after occlusion. Histological specimens were examined 24 hours after occlusion. In Group Y, rCBF did not change significantly after venous occlusion. However, in Group A, rCBF decreased rapidly beginning 15 minutes after occlusion. Significant intergroup differences were observed 30, 60, and 90 minutes after occlusion. Venous flow arrest, which resulted in venous infarct, was observed on angiography 90 minutes after occlusion in two (10.5%) of 19 young and six (85.7%) of seven aged rats. The venous thrombus in Group A rats was significantly larger than that in Group Y rats 90 minutes after occlusion. Venous infarction was seen in all aged rats (100%) and in six young rats (31.6%); the infarct size, expressed as a percentage of the size of the ipsilateral hemisphere, was significantly larger in aged rats than in young rats.Conclusions. This study demonstrated an age-related increase in the rate and size of venous infarct following vein occlusion, suggesting that the greater vulnerability to CVCDs in the aged brain might be attributed to early and extensive hypoperfusion of circumscribed brain areas drained by the occluded vein. The larger thrombus formation in aged animals indicates that a shift in the thrombogenetic/thrombolytic equilibrium is responsible for the observed effect.

scholarly journals Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

2011 ◽  
Vol 300 (4) ◽  
pp. R1001-R1008 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Connie L. Grobe ◽  
Terry G. Beltz ◽  
Alan Kim Johnson
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Aged Rats ◽  
Middle Aged ◽  
Young Rats ◽  
Arterial Blood ◽  
Age Related ◽  
Old Rats

These experiments examined water-drinking and arterial blood pressure responses to β-adrenergic receptor activation in young (4 mo), “middle-aged” adult (12 mo), and old (29 mo) male rats of the Brown-Norway strain. We used isoproterenol to simultaneously activate β1- and β2-adrenergic receptors, salbutamol to selectively activate β2-adrenergic receptors, and the combination of isoproterenol and the β2-adrenergic receptor antagonist ICI 118,551 to stimulate only β1-adrenergic receptors. Animals received one of the drug treatments, and water drinking was measured for 90 min. About 1 wk later, animals received the same drug treatment for measurement of arterial blood pressure responses for 90 min. In some rats, levels of renin and aldosterone secretion in response to isoproterenol or salbutamol were measured in additional tests. Old and middle-aged rats drank significantly less after isoproterenol than did young rats and also had greater reductions in arterial blood pressure. Old and middle-aged rats drank significantly less after salbutamol than did young rats, although reductions in arterial blood pressure were equivalent across the ages. The β2-adrenergic antagonist ICI 118,551 abolished drinking after isoproterenol and prevented most of the observed hypotension. Renin secretion after isoproterenol and salbutamol was greater in young rats than in middle-aged rats, and wholly absent in old rats. Aldosterone secretion was reduced in old rats compared with young and middle-aged rats after treatment with isoproterenol, but not after treatment with salbutamol. In conclusion, there are age-related differences in β-adrenergic receptor-mediated drinking that can be explained only in part by age-related differences in renin secretion after β-adrenergic receptor stimulation.

scholarly journals Hypotension- and osmotically induced thirst in old Brown Norway rats

2009 ◽  
Vol 297 (1) ◽  
pp. R149-R157 ◽  
Author(s):  
Robert L. Thunhorst ◽  
Terry G. Beltz ◽  
Alan Kim Johnson
Keyword(s):  
Arterial Pressure ◽  
Brown Norway ◽  
Aged Rats ◽  
Middle Aged ◽  
Young Rats ◽  
Age Related ◽  
Cellular Dehydration ◽  
Old Rats ◽  
Middle Aged Adult ◽  
Norway Rats

Compared to young cohorts, old rats drink less water in response to several thirst-inducing stimuli. In these experiments, we characterized water drinking in response to hypotension and cellular dehydration in young (4 mo), middle-aged adult (12 mo) and old (29–30 mo) male Brown Norway rats. We injected the vasodilator, minoxidil as an intravenous bolus in a range of doses (0–20 mg/kg), so that drinking responses could be compared at equivalent reductions of arterial pressure. Old rats had greatly diminished reflex tachycardia and became significantly more hypotensive after minoxidil compared with young and middle-aged rats. When compared at equivalent reductions of arterial pressure, old rats drank one-third as much as middle-aged rats, and one-fifth as much as young rats. In addition, there were age-related deficits in drinking in response to a range of administered loads of sodium (0.15–2 M NaCl, 2 ml/100 g body wt). Urinary excretion of water and sodium in response to the loads was equivalent across ages. Both middle-aged and old rats were less able than young rats to repair their water deficits after sodium loading, attributable almost entirely to their reduced drinking responses compared with young rats. Lastly, age-related declines in drinking appeared to be more severe in response to hypotension than in response to cellular dehydration.

scholarly journals Animal models of memory impairment

1997 ◽  
Vol 352 (1362) ◽  
pp. 1711-1717 ◽  
Author(s):  
◽  
Michela Gallagher
Keyword(s):  
Animal Models ◽  
Spatial Memory ◽  
Memory Impairment ◽  
Structural Integrity ◽  
Hippocampal Formation ◽  
Cholinergic Neurons ◽  
The Elderly ◽  
Aged Rats ◽  
Young Rats ◽  
Age Related

Memory impairment in the elderly resembles a mild temporal lobe dysfunction. Alterations in the hippocampal formation are also a probable basis for cognitive deficits in some animal models of ageing. For example, aged rats are impaired in hippocampal-dependent tests of spatial memory. Recent studies have revealed considerable structural integrity in the aged hippocampus, even in aged rats with the most impaired spatial memory. In contrast, atrophy/loss of cholinergic neurons in the basal forebrain and deficiency in cholinergic transduction in hippocampus correlate with the severity of spatial memory impairment in aged rats. This evidence supports the longstanding view that age-related loss of memory has a cholinergic basis. In this context, it is somewhat surprising that the use of a selective cholinergic immunotoxin in young rats to further test this hypothesis has revealed normal spatial memory after removing septo-hippocampal cholinergic neurons. Young rats with immunotoxic lesions, however, have other behavioural impairments in tests of attentional processing. These lines of research have implications for understanding the neurobiological basis of memory deficits in ageing and for selecting an optimal behavioural setting in which to examine therapies aimed at restoring neurobiological function.

Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli

1996 ◽  
Vol 76 (5) ◽  
pp. 3114-3125 ◽  
Author(s):  
P. S. Palombi ◽  
D. M. Caspary
Keyword(s):  
Inferior Colliculus ◽  
Response Pattern ◽  
Aged Rats ◽  
Temporal Response ◽  
Fischer 344 ◽  
Young Rats ◽  
Age Related ◽  
Intensity Functions ◽  
F344 Rats ◽  
Age Related Changes

1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.

scholarly journals Aging Impairs Endocytic Capacity Of Splenic Dendritic Cells From Dark Agouti Rats And Alters Their Response To TLR4 Stimulation

2015 ◽  
Vol 65 (1) ◽  
pp. 30-55 ◽  
Author(s):  
BUFAN Biljana ◽  
STOJIĆ-VUKANIĆ Zorica ◽  
DJIKIĆ Jasmina ◽  
KOSEC Duško ◽  
PILIPOVIĆ Ivan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Relative Proportion ◽  
Dark Agouti ◽  
Aged Rats ◽  
Adult Rats ◽  
Young Rats ◽  
Age Related ◽  
Age Related Changes

Abstract The study was undertaken considering: i) that relative proportion of distinct subsets of splenic dendritic cells (DCs) is strain-specific and predictive for the susceptibility to autoimmune diseases; ii) age-related changes in endocytic, allostimulatory and polarizing capacity of splenic OX62+ DCs from Albino Oxford rats (relatively resistant to Th1/Th17-mediated diseases) and iii) strain specificities in age-related changes of mouse DCs. To ascertain whether there are strain specificities in age-related rat DC changes, we examined the influence of aging on OX62+ DCs from Dark Agouti (DA) rats prone to Th1/Th17-mediated autoimmune diseases. The study provided additional evidence that the predominance of CD4-cells within OX62+ DCs from young adult rats correlates with their susceptibility to Th1/Th17-mediated diseases. Consistently, lipopolysaccharide (LPS)-matured DCs from 3-month-old (young) rats exhibited Th1 driving force when co-cultured with allogeneic CD4+ T cells. This most likely reflected enhanced TNF-α and iNOS expression. Comparing with young rats, OX62+ DCs from 26-month-old (aged) rats showed: i) diminished endocytic capacity; ii) impaired ability to mature in vitro upon LPS stimulation (as indicated by lower MHC II, CD86 and CD40 surface expression), which is consistent with the increase in their IL-10 production, and iii) diminished allostimulatory capacity and loss of Th1-driving capacity in the mixed lymphocyte reaction. The latter, probably, reflected greater IL-10 production by LPS-stimulated DC from aged rats, as well as lower CD40 density on their surface. Overall, our findings suggest that aging might affect DA rat capability to mount an efficient Th1 immune response, and consequently susceptibility to Th1/Th17-mediated pathology.

Age-related changes in the responsiveness of apolipoprotein A1 to thyroid hormone

1996 ◽  
Vol 271 (6) ◽  
pp. R1602-R1607
Author(s):  
A. D. Mooradian ◽  
N. C. Wong ◽  
G. N. Shah
Keyword(s):  
Thyroid Hormone ◽  
Statistical Significance ◽  
Fold Increase ◽  
Binding Activity ◽  
Apolipoprotein A1 ◽  
Aged Rats ◽  
Mobility Shift ◽  
Young Rats ◽  
Age Related ◽  
Age Related Changes

To determine the age-related changes in the effect of thyroid hormone on apolipoprotein A1 (ApoA1) gene expression, male Fischer 344 rats at 4 (young) and 26 (aged) mo of age were studied. Hyperthyroidism was induced with daily intraperitoneal injections of 3,5,3'-triiodothyronine (15 micrograms/100 g body wt) for 10 days. Hypothyroidism was induced with 0.025% methimazole in drinking water for 4 wk. Hyperthyroidism was associated with increased serum ApoA1 levels in young rats [7.52 +/- 0.41 vs. 3.67 +/- 0.30 optical density (OD); P < 0.01]. The increase in aged rats (6.5 +/- 0.87 vs. 5.14 +/- 0.09 OD) did not reach statistical significance. Hypothyroidism was not associated with significant changes in serum ApoA1 levels in either young or aged rats. Hyperthyroidism was associated with a 2.5-fold increase in ApoA1 mRNA in young rats and a 1.7-fold increase in aged rats. Hypothyroidism was associated with a 3.6-fold reduction in ApoA1 mRNA in young rats, but there was no significant change in aged hypothyroid rats. Mobility shift assays indicated that the binding of transacting factors to ApoA1 promoter increased in hyperthyroid young rats but not in hyperthyroid aged rats. It is concluded that aging in rats is associated with reduced ApoA1 responsiveness to thyroid hormones. This altered responsiveness could partly be the result of changes in the binding activity of nuclear factors to the ApoA1 promoter.

Eplerenone Reverses Age-Dependent Cardiac Fibrosis Through Downregulating Osteopontin

2021 ◽  
Author(s):  
Mahshid Malakootian ◽  
Majid Maleki ◽  
Negar Mohammadian ◽  
Maedeh Arabian
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Expression Level ◽  
Aged Rats ◽  
Geriatric Population ◽  
Functional Changes ◽  
Young Rats ◽  
New Therapeutic Approaches ◽  
Age Related ◽  
Age Dependent

Abstract Background: The risk of cardiovascular disease dramatically increases with Ageing. Nowadays it is fully revealed that the fibrotic remodelling is the main cause of cardiac structural and functional changes related to the normal aging process, but the related signaling pathways and mechanisms are incompletely understood. Thus finding the new therapeutic approaches targeting cardiac fibrotic remodelling, may be necessary to develop preventive care in geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as novel mediators of age-dependent fibrotic pathways in heart as well as the effect of eplerenone on cardiac fibrosis reversal. Methods: Fischer-344 (F-344) rats has been used as three groups: young rats (2–3months old), aged rats (22-24 months old) without any treatment and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The expression level of OPN has been evaluated using real-time PCR and histological assessments were done to assess cardiac tissue fibrosis.Results: The expression level of OPN in aged rats was significantly higher than young rats and treatment with eplerenone significantly attenuated the level of OPN as well as cardiac fibrosis compare to untreated aged rats. Conclusion: Targeting cardiac fibroblast function with eplerenone could decrease expression of OPN marker and cause to reversal age-related cardiac fibrotic changes.

scholarly journals High doses of minocycline may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction

2018 ◽  
Vol 46 (4) ◽  
pp. 1404-1413 ◽  
Author(s):  
Wenyao Li ◽  
Qing Chai ◽  
Hongwei Zhang ◽  
Jing Ma ◽  
Chengfen Xu ◽  
...  
Keyword(s):  
Abdominal Surgery ◽  
Cognitive Dysfunction ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Postoperative Cognitive Dysfunction ◽  
Morris Water Maze Test ◽  
High Morbidity ◽  
Mrna Levels ◽  
Aged Rats ◽  
High Doses

Objective Postoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1 day, 3 days, and 7 days after surgery, and microglial activation was measured at 3 hours and 7 days after surgery. Memory was assessed using the Morris water maze test. Results Surgery resulted in severe cognitive impairment in aged rats and induced a significant neuroinflammatory response and microglial activation. The use of minocycline can prevent microglial activation after surgery, but delayed microglial activation may occur. The use of minocycline may further impair memory after surgery. Conclusion Minocycline can restrain microglial activation and restrict the inflammatory response in the hippocampus early after surgery, but it may induce delayed microglial activation and cannot prevent POCD in aged rats.

scholarly journals Age Impacts the Burden That Reference Memory Imparts on an Increasing Working Memory Load and Modifies Relationships With Cholinergic Activity

2021 ◽  
Vol 15 ◽  
Author(s):  
Victoria E. Bernaud ◽  
Ryoko Hiroi ◽  
Mallori L. Poisson ◽  
Arthur J. Castaneda ◽  
Ziv Z. Kirshner ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Load ◽  
Reference Memory ◽  
Female Rats ◽  
Aged Rats ◽  
Working Memory Load ◽  
Cholinergic Activity ◽  
Aging Research ◽  
Young Rats ◽  
Age Related

Rodent aging research often utilizes spatial mazes, such as the water radial-arm-maze (WRAM), to evaluate cognition. The WRAM can simultaneously measure spatial working and reference memory, wherein these two memory types are often represented as orthogonal. There is evidence, however, that these two memory forms yield interference at a high working memory load. The current study systematically evaluated whether the presence of a reference memory component impacts handling of an increasing working memory load. Young and aged female rats were tested to assess whether aging impacts this relationship. Cholinergic projections from the basal forebrain to the hippocampus and cortex can affect cognitive outcomes, and are negatively impacted by aging. To evaluate whether age-related changes in working and reference memory profiles are associated with cholinergic functioning, we assessed choline acetyltransferase activity in these behaviorally-tested rats. Results showed that young rats outperformed aged rats on a task testing solely working memory. The addition of a reference memory component deteriorated the ability to handle an increasing working memory load, such that young rats performed similar to their aged counterparts. Aged rats also had challenges when reference memory was present, but in a different context. Specifically, aged rats had difficulty remembering which reference memory arms they had entered within a session, compared to young rats. Further, aged rats that excelled in reference memory also excelled in working memory when working memory demand was high, a relationship not seen in young rats. Relationships between cholinergic activity and maze performance differed by age in direction and brain region, reflecting the complex role that the cholinergic system plays in memory and attentional processes across the female lifespan. Overall, the addition of a reference memory requirement detrimentally impacted the ability to handle working memory information across young and aged timepoints, especially when the working memory challenge was high; these age-related deficits manifested differently with the addition of a reference memory component. This interplay between working and reference memory provides insight into the multiple domains necessary to solve complex cognitive tasks, potentially improving the understanding of complexities of age- and disease- related memory failures and optimizing their respective treatments.

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